The hypothesis that N-nitroso compounds are carcinogenic because they are converted to direct alkylating agents by only target tissues is attractive, but most studies designed to test the hypothesis have investigated formation of alkylated bases only after a single administration of a near lethal dose of carcinogen. Current studies are examining quantitatively the nature and extent of alkylation of nucleic acids in liver, kidney, lung, pancreas and colon by five carcinogens which are converted to alkylating agents at widely different rates by these tissues. Sensitivities of these to the carcinogenic activity of diethylnitrosamine, N-nitrosopyrrolidine, N-Nitrosomorpholine, methylnitrosourea, and 1,2-dimethylhydrazine are established and are being used as comparators with sites of alkylation. Adult rats, hamsters, or guinea pigs are given single injections of carcinogen and isolated nucleic acids are hydrolyzed and assayed for at least seven alkylated bases including 0-6-methylguanine by liquid chromatography. Dose-response characteristics are determined for each alkylated base and compared to known sensitivities of each tissue to the carcinogens. Changes in the extent to which alkylation at specific sites occurs will be determined in rats exposed continuously to carcinogenic doses of 1,2-dimethylhydrazine, diethylnitrosamine, and nitrosomorpholine during the tumor induction period. Comparisons similar to those in the acute studies will be made.